Advertisement

Brain Natriuretic Peptide is Not Reno-Protective during Renal Ischemia-Reperfusion Injury in the Rat1

      Background

      Acute kidney injury (AKI) occurs in 30% of patients undergoing complex cardiovascular surgery, and renal ischemia-reperfusion (I/R) injury is often a contributing factor. A recent meta-analysis observed that perioperative natriuretic peptide administration was associated with a reduction in AKI requiring dialysis in cardiovascular surgery patients. This study was designed to further clarify the potential reno-protective effect of brain natriuretic peptide (BNP) using an established rat model of renal I/R injury.

      Methods

      The study comprised three groups (n = 10 kidneys each): (1) control (no injury); (2) I/R injury (45 min of bilateral renal ischemia followed by 3 h of reperfusion); and (3) BNP (I/R injury plus rat-BNP pretreatment at 0.01 μg/kg/min). Glomerular filtration rate (GFR) and a biomarker of AKI, urinary neutrophil gelatinase-associated lipocalin (uNGAL), were measured at baseline and at 30 minute intervals post-ischemia. Groups were compared using two-way repeated measures analysis of variance (mean ± SD, significance P < 0.05).

      Results

      Baseline GFR measurements for control, I/R, and BNP groups were 1.07 ± 0.55, 0.88 ± 0.51, and 1.03 ± 0.59 mL/min (P = 0.90), respectively. Post-ischemia, GFR was significantly lower in I/R and BNP compared with controls at 30 min, 1.29 ± 0.97, 0.08 ± 0.04, and 0.06 ± 0.05 mL/min (P < 0.01), and remained lower through 3 h, 1.79 ± 0.44, 0.30 ± 0.17, and 0.32 ± 0.12 mL/min (P < 0.01). Comparing I/R to BNP groups, GFR did not differ significantly at any time point. There was no significant difference in uNGAL levels at 1 h (552 ± 358 versus 516 ± 259 ng/mL, P = 0.87) or 2 h (1073 ± 589 versus 989 ± 218 ng/mL, P = 0.79) between I/R and BNP.

      Conclusions

      BNP does not reduce the renal injury biomarker, urinary NGAL, or preserve GFR in acute renal ischemia-reperfusion injury.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Surgical Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Shimada M.
        • Ejaz A.A.
        • Beaver T.M.
        Role of natriuretic peptides in cardiovascular surgery.
        Expert Rev Cardiovasc Ther. 2009; 7: 515
        • Lanese D.M.
        • Yuan B.H.
        • Falk S.A.
        • et al.
        Effects of atriopeptin III on isolated rat afferent and efferent arterioles.
        Am J Physiol. 1991; : F1102
        • Chujo K.
        • Ueki M.
        • Asaga T.
        • et al.
        Atrial natriuretic peptide attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats.
        Tohoku J Exp Med. 2008; 215: 257
        • Beaver T.M.
        • Winterstein A.G.
        • Shuster J.J.
        • et al.
        Effectiveness of nesiritide on dialysis or all-cause mortality in patients undergoing cardiothoracic surgery.
        Clin Cardiol. 2006; 29: 18
        • Mentzer Jr., R.M.
        • Oz M.C.
        • Sladen R.N.
        • et al.
        NAPA Investigators. Effects of perioperative nesiritide in patients with left ventricular dysfunction undergoing cardiac surgery: The NAPA Trial.
        J Am Coll Cardiol. 2007; 49: 716
        • Swärd K.
        • Valsson F.
        • Odencrants P.
        • et al.
        Recombinant human atrial natriuretic peptide in ischemic acute renal failure: A randomized placebo-controlled trial.
        Crit Care Med. 2004; 32: 1310
        • Ejaz A.A.
        • Martin T.D.
        • Johnson R.J.
        • et al.
        Prophylactic nesiritide does not prevent dialysis or all-cause mortality in patients undergoing high-risk cardiac surgery.
        J Thorac Cardiovasc Surg. 2009; 138: 959
        • Nigwekar S.U.
        • Hix J.K.
        The role of natriuretic peptide administration in cardiovascular surgery-associated renal dysfunction: A systematic review and meta-analysis of randomized controlled trials.
        J Cardiothorac Vasc Anesth. 2009; 23: 151
        • Chertow G.M.
        • Lazarus J.M.
        • Christiansen C.L.
        • et al.
        Preoperative renal risk stratification.
        Circulation. 1997; 95: 878
        • Mangano C.M.
        • Diamondstone L.S.
        • Ramsay J.G.
        • et al.
        Renal dysfunction after myocardial revascularization: Risk factors, adverse outcomes, and hospital resource utilization.
        Ann Intern Med. 1998; 128: 194
        • Rosner M.H.
        • Okusa M.D.
        Acute kidney injury associated with cardiac surgery.
        Clin J Am Soc Nephrol. 2006; 1: 19
        • Arnaoutakis G.J.
        • Bihorac A.
        • Martin T.D.
        • et al.
        RIFLE criteria for acute kidney injury in aortic arch surgery.
        J Thorac Cardiovasc Surg. 2007; 134: 1554
        • Levy E.M.
        • Viscoli C.M.
        • Horwitz R.I.
        The effect of acute renal failure on mortality. A cohort analysis.
        JAMA. 1996; 275: 1489
        • Bellomo R.
        • Ronco C.
        • Kellum J.A.
        • et al.
        Acute Dialysis Quality Initiative workgroup. Acute renal failure-definition, outcome measures, animal models, fluid therapy, and information technology needs: The Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.
        Crit Care. 2004; 8: R204
        • Bellomo R.
        • Auriemma S.
        • Fabbri A.
        • et al.
        The pathophysiology of cardiac-surgery associated acute kidney injury (CSA-AKI).
        Int J Artif Organs. 2008; 31: 166
        • Coca S.G.
        • Yalavarthy R.
        • Concato J.
        • et al.
        Biomarkers for the diagnosis and risk stratification of acute kidney injury: A systematic review.
        Kidney Int. 2008; 73: 1008
        • Mishra J.
        • Ma Q.
        • Prada A.
        • et al.
        Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury.
        J Am Soc Nephrol. 2003; 14: 2534
        • Mishra J.
        • Dent C.
        • Tarabishi R.
        • et al.
        Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery.
        Lancet. 2005; 365: 1231
        • Ren B.
        • Shen Y.
        • Shao H.
        • et al.
        Brain natriuretic peptide limits myocardial infarct size dependent of nitric oxide synthase in rats.
        Clin Chim Acta. 2007; 377: 83
        • Kennedy S.E.
        • Ehrlich J.H.
        Murine renal ischemia-reperfusion injury.
        Nephrology (Carlton). 2008; 13: 390
        • Awad A.S.
        • Rouse M.
        • Huang L.
        • et al.
        Compartmentalization of neutrophils in the kidney and lung following acute ischemic kidney injury.
        Kidney Int. 2009; 75: 689
        • Bihorac A.
        • Yavas S.
        • Subbiah S.
        • et al.
        Long-term risk of mortality and acute kidney injury during hospitalization after major surgery.
        Ann Surg. 2009; 249: 851
        • Hobson C.E.
        • Yavas S.
        • Segal M.S.
        • et al.
        Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery.
        Circulation. 2009; 119: 2444